A murine alpha-2 macroglobulin (AMG) purified from both tumor ascites and normal plasma has been shown to carry 3 separate activities: protease-binding, immunosuppresive (ISP) and tumor-inhibiting (TI) activities. The ISP and TI activities can be dissociated and isolated from AMG which is a protease-inhibitor. Current investigation attempts to purify ISP and TI factors and to elucidate their mechanisms of inhibitory action of AMG on neoplastic cells and lymphocytes. The efficacy of employing TI factor as an anti-tumor therapeutic agent is also being investigated. Concurrently, we are also studying an immunostimulatory (IST) "macro-globulin" specifically associated with the spontaneously regressing subline of lymphoma L1210. This IST factor can specifically stimulate only the secondary antibody (IgM, IgG1, IgG2, IgG3) responses of mice against sheep red blood cell antigens. Its effects on other immune effector functions and its roles in spontaneous tumor regression are being investigated. Current investigation attempts to purify this factor and to identify specific immune reactions important for the spontaneous regression of tumors.